Chronic Lymphocytic Leukemia, Diffuse Large B-cell Lymphoma, Follicular Lymphoma, High-grade B-cell Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Primary Mediastinal Large B-cell Lymphoma, Small Lymphocytic Lymphoma
Conditions
Keywords
Anti-CD37, monoclonal antibodies, DuoHexabody®
Brief summary
The drug that will be investigated in the study is an antibody, GEN3009. Since this is the first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3009 dose to be tested in a larger group of patients and assess preliminary clinical activity of GEN3009. GEN3009 will be studied in a broad group of cancer patients, having different kinds of lymphomas. All patients will get GEN3009 either as a single treatment (monotherapy) or in combination with another antibody-candidate for treatment of cancer in the blood. The study consists of two parts: Part 1 tests increasing doses of GEN3009 (escalation), followed by Part 2 which tests the recommended GEN3009 dose from Part 1 (expansion).
Detailed description
This trial will be conducted in 2 parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). All subjects in Part 1 will receive GEN3009, administered at various dose levels in 28-day cycles. Dose Limiting Toxicity (DLT) will be assessed during the first treatment cycle of Part 1 and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be identified. Subjects in Part 2 will be treated with the Part 1-defined RP2D of GEN3009. Some subjects will receive GEN3009 in combination of a fixed dose of another antibody-candidate. Subjects in Part 2 are assigned either to one of 3 groups: Part 2 Monotherapy (hereafter referred to as 'Part 2A'), Part 2 Combination Safety Run-in ('Part2B') or Part 2 Combination ('Part2C'). Various types of B-cell NHLs are studied, including diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (HGBCL), mantle cell lymphoma (MCL), primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Interventions
BIOLOGICALGEN3009
GEN3009 will be administered by intravenous (IV) infusion in cycles of 28 days
BIOLOGICALEpcoritamab
Epcoritamab will be administered by subcutaneous (SC) injections in cycles of 28 days
Sponsors
Genmab
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Be at least 18 years of age. 2. Must sign an informed consent form prior to any screening procedures. 3. Dose Escalation: Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, the experimental therapy may be beneficial. All subjects must have received at least two prior lines of systemic therapy. Dose Expansion: Has histologically or cytologically confirmed relapsed or refractory B-cell NHL. All subjects must have received at least 2 prior lines of systemic therapy, and, 1. For FL and DLBCL, at least 1 of the 2 prior lines of treatment must have been a CD20 containing systemic regimen; 2. For CLL, subjects must have received at least one prior line of BTK inhibitor or BCL 2 inhibitor. 4. Has one of the eligible subtypes of B-cell NHL : Dose Escalation: (DLBCL, HGBCL, PMBCL, FL, MCL, MZL, SLL, or CLL). Dose Expansion: (DLBCL, FL, CLL) 5. Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic Leukemia (CLL). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Has adequate hepatic, renal, and bone marrow functions. 8. Before the first dose of GEN3009, during the trial, and for 12 months after the last dose of GEN3009 and/or the combination, a woman must be either not of childbearing potential or of childbearing potential and practicing a highly effective method of birth control, and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening. 9. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control. 10. Subjects must have a life expectancy of at least 3 months. Key
Exclusion criteria
1. Prior treatment with a CD37-targeting agent. 2. Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT). 3. Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort only). 4. Autologous HSCT within 3 months before the first dose of GEN3009. 5. Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal cells in the peripheral blood indicating circulating lymphoma cells. 6. Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009. Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K inhibitors within 5 half-lives prior to the first dose of GEN3009. 7. Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009. 8. Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009, and at any time during the study treatment period. 9. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy. 10. Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2-week period before the first dose of GEN3009. 11. Has uncontrolled intercurrent illness. 12. Seizure disorder requiring therapy (such as steroids or anti-epileptics) (Combination Expansion cohort only). 13. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy. 14. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening. 15. Known past or current malignancy other than inclusion diagnosis. 16. Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or intolerant to GEN3009 or to the combination therapy excipients. 17. Has had major surgery within 4 weeks before screening or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the trial (or within 4 weeks after the last dose of GEN3009 and/or the combination therapy). 18. Known history/positive serology for hepatitis B. 19. Known medical history or ongoing hepatitis C infection that has not been cured. 20. Known history of seropositivity for HIV infection. 21. Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or the combination therapy. 22. Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or the combination therapy. 23. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Additionally, vulnerable subjects or subjects under guardianship, curatorship, judicial protection or deprived of liberty), are excluded from participation in this trial. 24. Exposed to live/live attenuated vaccine within 4 weeks prior to initiation of GEN3009 treatment. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | During the first treatment cycle (Cycle length=28 days) | DLTs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, except for TLS (Cairo-Bishop grading) and CRS/ICANS (Lee et al., 2019). These criteria include: all Grade 5 toxicities; hematologic events including thrombocytopenia Grade 4, neutropenia Grade 4, Febrile neutropenia Grade 3 or 4, Grade 3 or 4 hemorrhage associated with thrombocytopenia of ≥Grade 3, anemia of Grade 4 and tumor lysis syndrome (TLS) Grade 4; and non-hematologic AEs of Grade 3 or higher excluding certain fevers, hypotension, laboratory values, Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), nausea, vomiting, diarrhea, fatigue/asthenia, or alopecia (no grading), which meet certain additional criteria. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | From first dose until 30 days after the last dose (up to 15.5 months) | An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as an AE that meets one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is medically significant\]); required inpatient hospitalization or prolongation of existing hospitalization. TEAEs are defined as AEs which begin, or worsen, during the on-treatment period ending 4 weeks after the last dose of study medication. |
| Number of Participants With AEs of Special Interest (AESI) | From first dose until 30 days after the last dose (up to 15.5 months) | AESIs are defined as events (serious or non-serious) that are of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate. |
| Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | From first dose until 30 days after the last dose (up to 15.5 months) | Laboratory parameters included hematology, serum chemistries and urinalysis. Clinically significant laboratory abnormalities were based upon the Investigator's discretion. Laboratory parameters captured as AEs are reported in this outcome measure. |
| Number of Participants With Clinically Notable Vital Signs | From first dose up to end of treatment (up to 14.5 months) | Criteria for clinically notable (elevated and below normal values respectively) vital signs are as follows: Systolic Blood Pressure (SBP): ≥180 millimeters of mercury (mmHg) and an increase ≥20 mmHg from baseline, ≤90 mmHg and a decrease ≥20 mmHg from baseline; Diastolic Blood Pressure (DBP): ≥105 mmHg and an increase ≥15 mmHg from baseline, ≤50 mmHg and a decrease ≥15 mmHg from baseline; Heart rate: ≥120 beats per minute (bpm) with an increase of ≥15 bpm from baseline, ≤50 bpm and a decrease ≥15 bpm from baseline; Temperature: \> 38 degree Celsius (°C) and \< 35°C. Number of participants with clinically notable elevated and below normal vital signs values up to end of treatment are reported. |
| Number of Participants With Dose Delays and Dose Interruptions | From first dose until 30 days after the last dose (up to 15.5 months) | Number of participants with dose delays and dose Interruptions due to AE, Coronavirus disease 2019 (COVID-19), drug administration issues and other unspecified reasons are reported. |
| Actual Dose Intensity | From first dose until 30 days after the last dose (up to 15.5 months) | Actual dose intensity (milligrams per cycle \[mg/cycle\]) is calculated as cumulative dose/number of cycles initiated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Concentrations (Ctrough) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| Terminal Elimination Half-Life (t 1/2) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) | From first dose until 30 days after the last dose (up to 15.5 months) | Venous blood samples will be collected for measurement of serum concentrations of ADAs. Number of participants with positive ADAs are reported in this outcome measure. The detection of ADAs was performed using validated, specific and sensitive Electrochemiluminescence Immunoassay (ECLIA) method. |
| Duration of Response (DoR) | From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months) | DoR is defined as the time from the first documentation of objective tumor response \[Complete response (CR) or Partial response (PR)\] to the date of first disease progression (PD) or death as assessed by the investigator based on Lugano criteria for B-cell non-Hodgkin lymphoma (B-cell NHL) and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) for chronic lymphocytic leukemia (CLL). Detailed definition of CR, PR and PD as per Lugano and iwCLL criteria in the protocol appendices. |
| Apparent Total Plasma Clearance (CL) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2 hours (h) and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| Progression-free Survival (PFS) | From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months) | PFS is defined as the time in days from Day 1 of Cycle 1 to the day of first documented PD, or the day of death due to any cause, whichever comes first as assessed by investigator based on Lugano Criteria for B-cell NHL and iwCLL for CLL. PFS was estimated using the Kaplan-Meier method. Detailed definitions of PD as per Lugano and iwCLL criteria in the protocol appendices. |
| Overall Survival (OS) | From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months) | The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. |
| Objective Response Rate (ORR) | From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months) | ORR: the percentage of participants who achieved a best overall response (BOR) of CR or PR as assessed by investigator based on Lugano Criteria for B-cell NHL and iwCLL for CLL. Detailed definitions of CR and PR as per Lugano and iwCLL criteria in the protocol appendices. |
| CR Rate | From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months) | CR rate was estimated using Clopper-Pearson method. Detailed definitions of CR as per Lugano and iwCLL criteria in the protocol appendices. |
| Time to Response (TTR) | From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months) | TTR: time from first dose of administration until date of first response as assessed by investigator based on Lugano criteria for B-cell NHL and iwCLL for CLL. It is derived for all participants who achieved PR or CR. Detailed definitions of CR, PR and PD as per Lugano and iwCLL criteria in the protocol appendices. |
| Volume of Distribution of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2 and 4 (S2 only); 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
| Time to Reach Cmax (Tmax) of GEN3009 | Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days) | — |
Countries
Belgium, Denmark, Netherlands, Spain, United States
Participant flow
Recruitment details
The study was conducted at investigative sites in Belgium, Denmark, France, Spain and the United States from 13 March 2020 to 28 July 2023.
Pre-assignment details
This study was to be conducted in 2 parts; Part 1 was the dose-escalation phase and Part 2 was the expansion phase. However, the trial was terminated due to strategic evaluation of GEN3009 within context of Genmab's portfolio, the sponsor decided not to conduct the expansion phase (Part 2).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: GEN3009 Dose Level A in S1 Participants received GEN3009 Dose level A in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. | 3 |
| Part 1: GEN3009 Dose Level B in S1 Participants received GEN3009 Dose level B in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. | 4 |
| Part 1: GEN3009 Dose Level C in S1 Participants received GEN3009 Dose level C in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. | 7 |
| Part 1: GEN3009 Dose Level D in S1 Participants received GEN3009 Dose level D in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. For cycle 1, participants received the dose split into 2 consecutive days. i.e., at C1D1 and the remaining amount at C1D2. | 10 |
| Part 1: GEN3009 Dose Level D in S2 Participants received GEN3009 Dose level D in S2 (in US only) by IV infusion on Days 1, 4, 8, 11, 15, 18, 22 and 25 in cycles 1, Day 1, 8, 15 and 22 in Cycles 2-3, Day 1 and 15 in Cycles 4-9 and Day 1 starting Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. Participants received half of the full dose on Days 1, 4, 8, 11, 15, 18, 22, and 25 i.e. two half doses on Days 1 and 4 of each week for the first cycle. | 3 |
| Part 1: GEN3009 Dose Level E in S1 Participants received GEN3009 Dose level E in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. For cycle 1, participants received the dose split into 2 consecutive days. i.e., at C1D1 and the remaining amount at C1D2. | 10 |
| Part 1: GEN3009 Dose Level F in S1 Participants received GEN3009 Dose level F in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. For cycle 1, participants received the dose split into 2 consecutive days. i.e., at C1D1 and the remaining amount at C1D2. | 3 |
| Part 1: GEN3009 Dose Level G in S1 Participants received GEN3009 Dose level G in S1 by IV infusion on Days 1, 8, 15, and 22 in cycles 1-3, on Days 1 and 15 in cycles 4-9 and on Day 1 (every 4 weeks) in Cycle 10 until disease progression, unacceptable toxicity, death or end of trial. Each cycle was 28 days in this study. For cycle 1, participants received the dose split into 2 consecutive days. i.e., at C1D1 and the remaining amount at C1D2. | 6 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 3 | 8 | 1 | 6 | 2 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Site is closing study participation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor request | 2 | 3 | 3 | 0 | 2 | 3 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: GEN3009 Dose Level A in S1 | Part 1: GEN3009 Dose Level B in S1 | Part 1: GEN3009 Dose Level C in S1 | Part 1: GEN3009 Dose Level D in S1 | Part 1: GEN3009 Dose Level D in S2 | Part 1: GEN3009 Dose Level E in S1 | Part 1: GEN3009 Dose Level F in S1 | Part 1: GEN3009 Dose Level G in S1 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 3.46 | 54.5 years STANDARD_DEVIATION 8.81 | 74.6 years STANDARD_DEVIATION 8.68 | 67.1 years STANDARD_DEVIATION 9.89 | 63.3 years STANDARD_DEVIATION 16.86 | 69.4 years STANDARD_DEVIATION 10.23 | 70.3 years STANDARD_DEVIATION 9.87 | 60.8 years STANDARD_DEVIATION 17.38 | 66.7 years STANDARD_DEVIATION 11.74 |
| Race/Ethnicity, Customized Ethnicity Missing | 0 Participants | 2 Participants | 5 Participants | 4 Participants | 0 Participants | 8 Participants | 3 Participants | 3 Participants | 25 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 6 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 18 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 2 Participants | 3 Participants | 7 Participants | 7 Participants | 3 Participants | 8 Participants | 3 Participants | 5 Participants | 38 Participants |
| Region of Enrollment Belgium | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Denmark | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 7 Participants |
| Region of Enrollment Netherlands | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Spain | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 10 Participants |
| Region of Enrollment United States | 3 Participants | 2 Participants | 2 Participants | 6 Participants | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 21 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 5 Participants | 8 Participants | 3 Participants | 8 Participants | 2 Participants | 5 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 4 | 3 / 7 | 8 / 10 | 1 / 3 | 6 / 10 | 2 / 3 | 3 / 6 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 7 / 7 | 9 / 10 | 3 / 3 | 10 / 10 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 | 4 / 7 | 7 / 10 | 2 / 3 | 4 / 10 | 2 / 3 | 4 / 6 |
Outcome results
Primary
Actual Dose Intensity
Actual dose intensity (milligrams per cycle \[mg/cycle\]) is calculated as cumulative dose/number of cycles initiated.
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009. 'Number analyzed' indicates the number of participants with data available for analysis at specified cycle duration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Actual Dose Intensity | Cycles 1-3 | 114.67 mg/cycle | Standard Deviation 112.1 |
| Part 1: GEN3009 Dose Level B in S1 | Actual Dose Intensity | Cycles 4-9 | 363.71 mg/cycle | — |
| Part 1: GEN3009 Dose Level B in S1 | Actual Dose Intensity | Cycles 1-3 | 720.00 mg/cycle | Standard Deviation 0 |
| Part 1: GEN3009 Dose Level C in S1 | Actual Dose Intensity | Cycle 10-until end of study | 318.94 mg/cycle | — |
| Part 1: GEN3009 Dose Level C in S1 | Actual Dose Intensity | Cycles 1-3 | 1389.46 mg/cycle | Standard Deviation 278.91 |
| Part 1: GEN3009 Dose Level C in S1 | Actual Dose Intensity | Cycles 4-9 | 799.71 mg/cycle | Standard Deviation 10.64 |
| Part 1: GEN3009 Dose Level D in S1 | Actual Dose Intensity | Cycles 1-3 | 2501.53 mg/cycle | Standard Deviation 992.91 |
| Part 1: GEN3009 Dose Level D in S1 | Actual Dose Intensity | Cycles 4-9 | 1527.27 mg/cycle | — |
| Part 1: GEN3009 Dose Level D in S2 | Actual Dose Intensity | Cycles 1-3 | 2515.85 mg/cycle | Standard Deviation 1053.9 |
| Part 1: GEN3009 Dose Level E in S1 | Actual Dose Intensity | Cycles 1-3 | 3903.62 mg/cycle | Standard Deviation 1135.72 |
| Part 1: GEN3009 Dose Level E in S1 | Actual Dose Intensity | Cycles 4-9 | 2400.00 mg/cycle | — |
| Part 1: GEN3009 Dose Level F in S1 | Actual Dose Intensity | Cycles 1-3 | 5957.23 mg/cycle | Standard Deviation 766.9 |
| Part 1: GEN3009 Dose Level F in S1 | Actual Dose Intensity | Cycles 4-9 | 2953.02 mg/cycle | Standard Deviation 349.28 |
| Part 1: GEN3009 Dose Level G in S1 | Actual Dose Intensity | Cycles 1-3 | 6973.78 mg/cycle | Standard Deviation 1072.58 |
Primary
Number of Participants With AEs of Special Interest (AESI)
AESIs are defined as events (serious or non-serious) that are of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate.
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With AEs of Special Interest (AESI) | 1 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With AEs of Special Interest (AESI) | 1 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With AEs of Special Interest (AESI) | 7 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With AEs of Special Interest (AESI) | 9 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With AEs of Special Interest (AESI) | 3 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With AEs of Special Interest (AESI) | 10 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With AEs of Special Interest (AESI) | 3 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With AEs of Special Interest (AESI) | 5 Participants |
Primary
Number of Participants With Clinically Notable Vital Signs
Criteria for clinically notable (elevated and below normal values respectively) vital signs are as follows: Systolic Blood Pressure (SBP): ≥180 millimeters of mercury (mmHg) and an increase ≥20 mmHg from baseline, ≤90 mmHg and a decrease ≥20 mmHg from baseline; Diastolic Blood Pressure (DBP): ≥105 mmHg and an increase ≥15 mmHg from baseline, ≤50 mmHg and a decrease ≥15 mmHg from baseline; Heart rate: ≥120 beats per minute (bpm) with an increase of ≥15 bpm from baseline, ≤50 bpm and a decrease ≥15 bpm from baseline; Temperature: \> 38 degree Celsius (°C) and \< 35°C. Number of participants with clinically notable elevated and below normal vital signs values up to end of treatment are reported.
Time frame: From first dose up to end of treatment (up to 14.5 months)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 1 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 2 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | Heart Rate: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Below Normal | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | DBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Below Normal | 1 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | SBP: Elevated | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Notable Vital Signs | Temperature: Elevated | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs
Laboratory parameters included hematology, serum chemistries and urinalysis. Clinically significant laboratory abnormalities were based upon the Investigator's discretion. Laboratory parameters captured as AEs are reported in this outcome measure.
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 2 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 1 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 1 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 1 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 1 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
Primary
Number of Participants With Dose Delays and Dose Interruptions
Number of participants with dose delays and dose Interruptions due to AE, Coronavirus disease 2019 (COVID-19), drug administration issues and other unspecified reasons are reported.
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 0 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 1 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 1 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 1 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 7 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 1 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 4 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 1 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 1 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 9 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 1 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 1 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 3 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 1 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 10 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 1 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 2 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 3 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 1 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 1 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to AE | 5 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to un-specified reason | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to unspecified reason | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose interruption due to drug administration issues | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to AE | 2 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Delays and Dose Interruptions | Dose delay due to Coronavirus disease 2019 (COVID-19) | 0 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, except for TLS (Cairo-Bishop grading) and CRS/ICANS (Lee et al., 2019). These criteria include: all Grade 5 toxicities; hematologic events including thrombocytopenia Grade 4, neutropenia Grade 4, Febrile neutropenia Grade 3 or 4, Grade 3 or 4 hemorrhage associated with thrombocytopenia of ≥Grade 3, anemia of Grade 4 and tumor lysis syndrome (TLS) Grade 4; and non-hematologic AEs of Grade 3 or higher excluding certain fevers, hypotension, laboratory values, Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), nausea, vomiting, diarrhea, fatigue/asthenia, or alopecia (no grading), which meet certain additional criteria.
Time frame: During the first treatment cycle (Cycle length=28 days)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as an AE that meets one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is medically significant\]); required inpatient hospitalization or prolongation of existing hospitalization. TEAEs are defined as AEs which begin, or worsen, during the on-treatment period ending 4 weeks after the last dose of study medication.
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Population: The Safety analysis set included all participants who had received at least 1 dose of GEN3009.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 4 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 7 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 4 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 10 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 7 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 10 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 4 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 6 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 4 Participants |
Secondary
Apparent Total Plasma Clearance (CL) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2 hours (h) and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The pharmacokinetic analysis set (PAS) includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level A in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level B in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level B in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level C in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level C in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level D in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level D in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level D in S2 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level D in S2 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level E in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level E in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level F in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
| Part 1: GEN3009 Dose Level F in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level G in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 1 | NA Liters per day |
| Part 1: GEN3009 Dose Level G in S1 | Apparent Total Plasma Clearance (CL) of GEN3009 | Cycle 2 | NA Liters per day |
Secondary
Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2 and 4 (S2 only); 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at a specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GEN3009 Dose Level C in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 1 | 159.2796 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 95.733 |
| Part 1: GEN3009 Dose Level C in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 2 | 132.6580 micrograms*day per milliliter(ug*day/mL) | — |
| Part 1: GEN3009 Dose Level D in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 2 | 159.3302 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 22.1333 |
| Part 1: GEN3009 Dose Level D in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 1 | 181.5966 micrograms*day per milliliter(ug*day/mL) | — |
| Part 1: GEN3009 Dose Level D in S2 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 1 | 260.8704 micrograms*day per milliliter(ug*day/mL) | — |
| Part 1: GEN3009 Dose Level E in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 1 | 219.1863 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 46.3749 |
| Part 1: GEN3009 Dose Level E in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 2 | 159.3456 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 98.0641 |
| Part 1: GEN3009 Dose Level F in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 2 | 363.4413 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 190.012 |
| Part 1: GEN3009 Dose Level F in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 1 | 353.5017 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 177.2169 |
| Part 1: GEN3009 Dose Level G in S1 | Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009 | Cycle 1 | 389.0321 micrograms*day per milliliter(ug*day/mL) | Standard Deviation 126.8407 |
Secondary
AUC From Time 0 to Infinity (AUCinf) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at a specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 6.0154 ug*day/mL | Standard Deviation 3.8503 |
| Part 1: GEN3009 Dose Level A in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 5.9939 ug*day/mL | Standard Deviation 0.6498 |
| Part 1: GEN3009 Dose Level B in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 56.3289 ug*day/mL | Standard Deviation 22.44 |
| Part 1: GEN3009 Dose Level B in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 46.4191 ug*day/mL | Standard Deviation 9.8966 |
| Part 1: GEN3009 Dose Level C in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 136.8615 ug*day/mL | Standard Deviation 72.7498 |
| Part 1: GEN3009 Dose Level C in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 139.9286 ug*day/mL | Standard Deviation 61.7235 |
| Part 1: GEN3009 Dose Level D in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 127.4566 ug*day/mL | Standard Deviation 49.8017 |
| Part 1: GEN3009 Dose Level D in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 163.9206 ug*day/mL | Standard Deviation 52.0135 |
| Part 1: GEN3009 Dose Level D in S2 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 332.1408 ug*day/mL | Standard Deviation 73.1435 |
| Part 1: GEN3009 Dose Level D in S2 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 957.4149 ug*day/mL | Standard Deviation 1427.7939 |
| Part 1: GEN3009 Dose Level E in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 192.0412 ug*day/mL | Standard Deviation 90.3476 |
| Part 1: GEN3009 Dose Level E in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 159.8668 ug*day/mL | Standard Deviation 73.6559 |
| Part 1: GEN3009 Dose Level F in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 2 | 363.7766 ug*day/mL | Standard Deviation 190.3613 |
| Part 1: GEN3009 Dose Level F in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 358.0010 ug*day/mL | Standard Deviation 183.3857 |
| Part 1: GEN3009 Dose Level G in S1 | AUC From Time 0 to Infinity (AUCinf) of GEN3009 | Cycle 1 | 335.8745 ug*day/mL | Standard Deviation 117.1831 |
Secondary
AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result. 'Number analyzed' indicates the number of participants with data available for analysis at specified cycle duration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 4.5524 ug*day/mL | Standard Deviation 2.3467 |
| Part 1: GEN3009 Dose Level A in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 4.4707 ug*day/mL | Standard Deviation 1.3098 |
| Part 1: GEN3009 Dose Level B in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 51.0701 ug*day/mL | Standard Deviation 17.1901 |
| Part 1: GEN3009 Dose Level B in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 45.0924 ug*day/mL | Standard Deviation 9.1404 |
| Part 1: GEN3009 Dose Level C in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 103.4129 ug*day/mL | Standard Deviation 73.3627 |
| Part 1: GEN3009 Dose Level C in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 121.5349 ug*day/mL | Standard Deviation 53.0658 |
| Part 1: GEN3009 Dose Level D in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 103.5413 ug*day/mL | Standard Deviation 61.7884 |
| Part 1: GEN3009 Dose Level D in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 148.4079 ug*day/mL | Standard Deviation 41.775 |
| Part 1: GEN3009 Dose Level D in S2 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 467.9622 ug*day/mL | Standard Deviation 283.7778 |
| Part 1: GEN3009 Dose Level D in S2 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 441.7798 ug*day/mL | Standard Deviation 542.0539 |
| Part 1: GEN3009 Dose Level E in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 150.7393 ug*day/mL | Standard Deviation 96.0893 |
| Part 1: GEN3009 Dose Level E in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 152.4631 ug*day/mL | Standard Deviation 74.104 |
| Part 1: GEN3009 Dose Level F in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 2 | 363.4413 ug*day/mL | Standard Deviation 190.012 |
| Part 1: GEN3009 Dose Level F in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 353.5017 ug*day/mL | Standard Deviation 177.2169 |
| Part 1: GEN3009 Dose Level G in S1 | AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009 | Cycle 1 | 327.1762 ug*day/mL | Standard Deviation 109.9472 |
Secondary
CR Rate
CR rate was estimated using Clopper-Pearson method. Detailed definitions of CR as per Lugano and iwCLL criteria in the protocol appendices.
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Population: The Response Evaluable set includes all participants in FAS who have baseline evaluable disease and had at least 1 post-baseline disease evaluation or died within 60 days of first trial treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | CR Rate | 0 percentage of participants |
| Part 1: GEN3009 Dose Level B in S1 | CR Rate | 0 percentage of participants |
| Part 1: GEN3009 Dose Level C in S1 | CR Rate | 28.6 percentage of participants |
| Part 1: GEN3009 Dose Level D in S1 | CR Rate | 0 percentage of participants |
| Part 1: GEN3009 Dose Level D in S2 | CR Rate | 33.3 percentage of participants |
| Part 1: GEN3009 Dose Level E in S1 | CR Rate | 0 percentage of participants |
| Part 1: GEN3009 Dose Level F in S1 | CR Rate | 33.3 percentage of participants |
| Part 1: GEN3009 Dose Level G in S1 | CR Rate | 0 percentage of participants |
Secondary
Duration of Response (DoR)
DoR is defined as the time from the first documentation of objective tumor response \[Complete response (CR) or Partial response (PR)\] to the date of first disease progression (PD) or death as assessed by the investigator based on Lugano criteria for B-cell non-Hodgkin lymphoma (B-cell NHL) and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) for chronic lymphocytic leukemia (CLL). Detailed definition of CR, PR and PD as per Lugano and iwCLL criteria in the protocol appendices.
Time frame: From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months)
Population: The FAS comprises all participants to whom study drug had been assigned and who had received at least 1 dose of GEN3009. 'Overall number of participants Analyzed' signified the participants who achieved CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GEN3009 Dose Level C in S1 | Duration of Response (DoR) | 15.9 months |
| Part 1: GEN3009 Dose Level D in S2 | Duration of Response (DoR) | NA months |
| Part 1: GEN3009 Dose Level E in S1 | Duration of Response (DoR) | 1.4 months |
| Part 1: GEN3009 Dose Level F in S1 | Duration of Response (DoR) | NA months |
| Part 1: GEN3009 Dose Level G in S1 | Duration of Response (DoR) | 4.1 months |
Secondary
Maximum Observed Plasma Concentration (Cmax) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result. 'Number analyzed' indicates the number of participants with data available for analysis at specified cycle duration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 8.3000 microgram per milliliter (ug/mL) | Standard Deviation 3.5355 |
| Part 1: GEN3009 Dose Level A in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 8.1050 microgram per milliliter (ug/mL) | Standard Deviation 3.6699 |
| Part 1: GEN3009 Dose Level B in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 43.4000 microgram per milliliter (ug/mL) | Standard Deviation 12.7674 |
| Part 1: GEN3009 Dose Level B in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 46.1667 microgram per milliliter (ug/mL) | Standard Deviation 2.7934 |
| Part 1: GEN3009 Dose Level C in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 89.8714 microgram per milliliter (ug/mL) | Standard Deviation 39.8257 |
| Part 1: GEN3009 Dose Level C in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 118.4800 microgram per milliliter (ug/mL) | Standard Deviation 29.9458 |
| Part 1: GEN3009 Dose Level D in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 147.4000 microgram per milliliter (ug/mL) | Standard Deviation 52.7286 |
| Part 1: GEN3009 Dose Level D in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 139.0000 microgram per milliliter (ug/mL) | Standard Deviation 43.8341 |
| Part 1: GEN3009 Dose Level D in S2 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 363.0667 microgram per milliliter (ug/mL) | Standard Deviation 460.6843 |
| Part 1: GEN3009 Dose Level D in S2 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 572.0000 microgram per milliliter (ug/mL) | Standard Deviation 708.4659 |
| Part 1: GEN3009 Dose Level E in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 144.4778 microgram per milliliter (ug/mL) | Standard Deviation 79.0905 |
| Part 1: GEN3009 Dose Level E in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 237.0000 microgram per milliliter (ug/mL) | Standard Deviation 30.8869 |
| Part 1: GEN3009 Dose Level F in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 2 | 394.6667 microgram per milliliter (ug/mL) | Standard Deviation 109.5871 |
| Part 1: GEN3009 Dose Level F in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 317.3333 microgram per milliliter (ug/mL) | Standard Deviation 51.4328 |
| Part 1: GEN3009 Dose Level G in S1 | Maximum Observed Plasma Concentration (Cmax) of GEN3009 | Cycle 1 | 352.6667 microgram per milliliter (ug/mL) | Standard Deviation 58.5514 |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADAs)
Venous blood samples will be collected for measurement of serum concentrations of ADAs. Number of participants with positive ADAs are reported in this outcome measure. The detection of ADAs was performed using validated, specific and sensitive Electrochemiluminescence Immunoassay (ECLIA) method.
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Population: The immunogenicity analysis set included all participants who had received at least 1 dose of study drug and had a baseline and at least 1 evaluable on-treatment ADA sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 1 Participants |
| Part 1: GEN3009 Dose Level B in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
| Part 1: GEN3009 Dose Level C in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 2 Participants |
| Part 1: GEN3009 Dose Level D in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
| Part 1: GEN3009 Dose Level D in S2 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
| Part 1: GEN3009 Dose Level E in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 1 Participants |
| Part 1: GEN3009 Dose Level F in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
| Part 1: GEN3009 Dose Level G in S1 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
Secondary
Objective Response Rate (ORR)
ORR: the percentage of participants who achieved a best overall response (BOR) of CR or PR as assessed by investigator based on Lugano Criteria for B-cell NHL and iwCLL for CLL. Detailed definitions of CR and PR as per Lugano and iwCLL criteria in the protocol appendices.
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Population: The Response Evaluable Set includes all participants in FAS who have baseline evaluable disease and had at least 1 post-baseline disease evaluation or died within 60 days of first trial treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Objective Response Rate (ORR) | 0 percentage of participants |
| Part 1: GEN3009 Dose Level B in S1 | Objective Response Rate (ORR) | 0 percentage of participants |
| Part 1: GEN3009 Dose Level C in S1 | Objective Response Rate (ORR) | 42.9 percentage of participants |
| Part 1: GEN3009 Dose Level D in S1 | Objective Response Rate (ORR) | 0 percentage of participants |
| Part 1: GEN3009 Dose Level D in S2 | Objective Response Rate (ORR) | 33.3 percentage of participants |
| Part 1: GEN3009 Dose Level E in S1 | Objective Response Rate (ORR) | 37.5 percentage of participants |
| Part 1: GEN3009 Dose Level F in S1 | Objective Response Rate (ORR) | 66.7 percentage of participants |
| Part 1: GEN3009 Dose Level G in S1 | Objective Response Rate (ORR) | 16.7 percentage of participants |
Secondary
Overall Survival (OS)
The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Population: The FAS comprises all participants to whom study drug had been assigned and who had received at least 1 dose of GEN3009.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Overall Survival (OS) | NA months |
| Part 1: GEN3009 Dose Level B in S1 | Overall Survival (OS) | NA months |
| Part 1: GEN3009 Dose Level C in S1 | Overall Survival (OS) | NA months |
| Part 1: GEN3009 Dose Level D in S1 | Overall Survival (OS) | 10.9 months |
| Part 1: GEN3009 Dose Level D in S2 | Overall Survival (OS) | NA months |
| Part 1: GEN3009 Dose Level E in S1 | Overall Survival (OS) | 13.7 months |
| Part 1: GEN3009 Dose Level F in S1 | Overall Survival (OS) | 13.1 months |
| Part 1: GEN3009 Dose Level G in S1 | Overall Survival (OS) | 6.6 months |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time in days from Day 1 of Cycle 1 to the day of first documented PD, or the day of death due to any cause, whichever comes first as assessed by investigator based on Lugano Criteria for B-cell NHL and iwCLL for CLL. PFS was estimated using the Kaplan-Meier method. Detailed definitions of PD as per Lugano and iwCLL criteria in the protocol appendices.
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Population: The FAS comprises all participants to whom study drug had been assigned and who had received at least 1 dose of GEN3009.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Progression-free Survival (PFS) | 1.4 months |
| Part 1: GEN3009 Dose Level B in S1 | Progression-free Survival (PFS) | 2.6 months |
| Part 1: GEN3009 Dose Level C in S1 | Progression-free Survival (PFS) | 4.3 months |
| Part 1: GEN3009 Dose Level D in S1 | Progression-free Survival (PFS) | 1.2 months |
| Part 1: GEN3009 Dose Level D in S2 | Progression-free Survival (PFS) | 2.3 months |
| Part 1: GEN3009 Dose Level E in S1 | Progression-free Survival (PFS) | 1.9 months |
| Part 1: GEN3009 Dose Level F in S1 | Progression-free Survival (PFS) | NA months |
| Part 1: GEN3009 Dose Level G in S1 | Progression-free Survival (PFS) | 0.8 months |
Secondary
Terminal Elimination Half-Life (t 1/2) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level A in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level B in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level B in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level C in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level C in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level D in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level D in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level D in S2 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level D in S2 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level E in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level E in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level F in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
| Part 1: GEN3009 Dose Level F in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level G in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 1 | NA days |
| Part 1: GEN3009 Dose Level G in S1 | Terminal Elimination Half-Life (t 1/2) of GEN3009 | Cycle 2 | NA days |
Secondary
Time to Reach Cmax (Tmax) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result. 'Number analyzed' indicates the number of participants with data available for analysis at specified cycle duration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 0.0765 days | Standard Deviation 0.012 |
| Part 1: GEN3009 Dose Level A in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.0445 days | Standard Deviation 0.0007 |
| Part 1: GEN3009 Dose Level B in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 0.1490 days | Standard Deviation 0.0957 |
| Part 1: GEN3009 Dose Level B in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.1650 days | Standard Deviation 0.1643 |
| Part 1: GEN3009 Dose Level C in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 0.2084 days | Standard Deviation 0.0553 |
| Part 1: GEN3009 Dose Level C in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.1656 days | Standard Deviation 0.082 |
| Part 1: GEN3009 Dose Level D in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.2740 days | Standard Deviation 0.301 |
| Part 1: GEN3009 Dose Level D in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 0.6039 days | Standard Deviation 0.6768 |
| Part 1: GEN3009 Dose Level D in S2 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 1.2123 days | Standard Deviation 1.5987 |
| Part 1: GEN3009 Dose Level D in S2 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.2030 days | Standard Deviation 0.0346 |
| Part 1: GEN3009 Dose Level E in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 0.5030 days | Standard Deviation 0.2908 |
| Part 1: GEN3009 Dose Level E in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.1620 days | Standard Deviation 0.0595 |
| Part 1: GEN3009 Dose Level F in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 2 | 0.1983 days | Standard Deviation 0.0535 |
| Part 1: GEN3009 Dose Level F in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 1.3817 days | Standard Deviation 0.089 |
| Part 1: GEN3009 Dose Level G in S1 | Time to Reach Cmax (Tmax) of GEN3009 | Cycle 1 | 1.2580 days | Standard Deviation 0.0771 |
Secondary
Time to Response (TTR)
TTR: time from first dose of administration until date of first response as assessed by investigator based on Lugano criteria for B-cell NHL and iwCLL for CLL. It is derived for all participants who achieved PR or CR. Detailed definitions of CR, PR and PD as per Lugano and iwCLL criteria in the protocol appendices.
Time frame: From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months)
Population: The FAS comprises all participants to whom study drug had been assigned and who had received at least 1 dose of GEN3009. 'Overall number of participants analyzed' indicates the number of participants who achieved CR or PR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GEN3009 Dose Level C in S1 | Time to Response (TTR) | 1.3361 months | Standard Deviation 0.1004 |
| Part 1: GEN3009 Dose Level D in S2 | Time to Response (TTR) | 1.8727 months | — |
| Part 1: GEN3009 Dose Level E in S1 | Time to Response (TTR) | 1.2704 months | Standard Deviation 0.2138 |
| Part 1: GEN3009 Dose Level F in S1 | Time to Response (TTR) | 2.0370 months | Standard Deviation 1.0222 |
| Part 1: GEN3009 Dose Level G in S1 | Time to Response (TTR) | 1.1828 months | — |
Secondary
Trough Concentrations (Ctrough) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level A in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level B in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level B in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level C in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level C in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level D in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level D in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level D in S2 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level D in S2 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level E in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level E in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level F in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
| Part 1: GEN3009 Dose Level F in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level G in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 2 | NA ug/mL |
| Part 1: GEN3009 Dose Level G in S1 | Trough Concentrations (Ctrough) of GEN3009 | Cycle 1 | NA ug/mL |
Secondary
Volume of Distribution of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Population: The PAS includes all participants who have been exposed to GEN3009 and have had at least one pharmacokinetic sample collected that has provided a valid bioanalytical result.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: GEN3009 Dose Level A in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level A in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level B in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level B in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level C in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level C in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level D in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level D in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level D in S2 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level D in S2 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level E in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level E in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level F in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |
| Part 1: GEN3009 Dose Level F in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level G in S1 | Volume of Distribution of GEN3009 | Cycle 1 | NA mL |
| Part 1: GEN3009 Dose Level G in S1 | Volume of Distribution of GEN3009 | Cycle 2 | NA mL |